Multicentre intraindividual randomized trial of topical methyl aminolaevulinate-photodynamic therapy vs. cryotherapy for multiple actinic keratoses on the extremities.

BACKGROUND: Methyl aminolaevulinate-photodynamic therapy (MAL-PDT) is an effective treatment in facial/scalp actinic keratosis (AK). OBJECTIVES: The aims of this study were to compare efficacy, safety, cosmetic outcome and patient preference of MAL-PDT vs. cryotherapy in patients with AK at other locations. METHODS: A multicentre, controlled, randomized, open, intraindividual, right-left comparison was performed. Patients with nonhyperkeratotic AK were treated once with MAL-PDT and cryotherapy on either side of the body. At week 12, lesions showing noncomplete response were retreated. The primary efficacy variable was the lesion response at week 24. Investigator's assessment of cosmetic outcome, patient's preference in terms of cosmetic outcome and a patient preference questionnaire were also analysed at week 24. RESULTS: In total, of 121 patients with 1343 lesions (98% located on the extremities and the remainder on the trunk and neck) were included. Both treatments provided a high mean percentage reduction in lesion count at week 24 with significantly higher efficacy for cryotherapy: 78% for MAL-PDT and 88% for cryotherapy (P=0.002, per protocol population). Investigator's assessment of cosmetic outcome was significantly better for MAL-PDT than cryotherapy (P<0.001), 79% of lesions having an excellent cosmetic outcome with MAL-PDT vs. 56% with cryotherapy at week 24. The cosmetic outcome achieved by MAL-PDT compared with cryotherapy was also preferred by patients (50% vs. 22%, respectively, P<0.001), and 59% of patients would prefer to have any new lesions treated with MAL-PDT compared with 25% with cryotherapy (P<0.001). Both treatment regimens were safe and well tolerated. CONCLUSIONS: MAL-PDT showed inferior efficacy for treatment of non-face/scalp AK compared with cryotherapy. However, both treatments showed high efficacy, and MAL-PDT conveyed the advantages of better cosmesis and higher patient preference.

Adapalene 0.1% gel has low skin-irritation potential.

BACKGROUND: Adapalene is a new naphthoic acid derivative with potent retinoid and antiinflammatory properties, developed for the topical treatment of acne vulgaris. OBJECTIVE: We compare the cutaneous safety of adapalene in different gel vehicles with tretinoin 0.025% gel. METHODS: A total of 42 healthy human subjects were enrolled in two randomized, double-blind, controlled, intraindividual studies. In the first study (study A), adapalene aqueous 0.03% and 0.1% gels were evaluated for their 21-day cumulative irritation potential compared with vehicle alone, patch alone, and tretinoin 0.025% gel under occlusion. In the second study (study B), adapalene aqueous (0.03% and 0.1%) gels and adapalene alcoholic (0.03% and 0.1%) gels were evaluated for their 5-day cumulative irritation potential compared with their respective vehicles and tretinoin 0.025% gel. Transepidermal water loss (TEWL) was measured daily at each visit. RESULTS: In study A, adapalene had a slight irritation potential that was in the same range as the gel vehicle and the patch alone, whereas tretinoin 0.025% gel was a severe irritant. In study B, no irritation was seen with either adapalene aqueous gels or adapalene gel vehicles or patch alone. The adapalene alcoholic gels were slightly irritating, and tretinoin gel produced intense irritation reactions in the majority of subjects. TEWL increased fourfold at the tretinoin site but remained unchanged at all adapalene sites. CONCLUSION: Adapalene 0.1% gel was significantly less irritating than tretinoin 0.025% gel.

Split-face comparison of adapalene 0.1% gel and tretinoin 0.025% gel in acne patients.

BACKGROUND: Adapalene is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. OBJECTIVE: We compared the skin tolerance of adapalene 0.1% gel with tretinoin 0.025% gel in subjects with acne. METHODS: Fifteen acne patient volunteers were enrolled in this investigator-masked, left-right comparison, randomized, controlled, intraindividual study. Adapalene 0.1% gel and tretinoin 0.025% gel were applied once a day to one half-face by the volunteers for 14 consecutive days. Clinical signs (erythema, desquamation, papules, vesicles, edema) and subjective symptoms (tightness, pruritus, burning) were evaluated and scored daily except on weekends. RESULTS: Adapalene 0.1% gel was better tolerated than tretinoin 0.025% gel. The overall mean score calculated from all features combined was significantly higher with tretinoin gel than with adapalene gel (p = 0.002). CONCLUSION: Adapalene 0.1% gel was significantly less irritating than tretinoin 0.025% gel when tested in acne patients.

Skin tolerance of adapalene 0.1% gel in combination with other topical antiacne treatments.

BACKGROUND: Adapalene (Differin gel) is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. OBJECTIVE: We assessed, in healthy volunteers, the skin irritancy potential of three combinations, each including adapalene 0.1% gel and one topical marketed antiacne product. METHODS: Twenty-five healthy volunteers were enrolled in a 21-day cumulative irritancy study performed in a double-blind, randomized, controlled, intraindividual design. Five days a week, the three materials (benzoyl peroxide, clindamycin phosphate, and erythromycin) were applied in a nonocclusive manner either alone or in combination with adapalene gel on seven cutaneous sites on the upper back. Adapalene was applied in the evening whereas the three other materials were applied in the morning. Irritation was evaluated and scored daily except on weekends. RESULTS: All materials were well-tolerated when tested alone. The combinations of adapalene 0.1% gel and either benzoyl peroxide, clindamycin phosphate, or erythromycin were also well-tolerated. The mean cumulative irritancy indices indicated that all three combinations were nonirritating. CONCLUSION: Under the conditions of the study, all tested treatments alone or in combination appeared nonirritating.

Adapalene 0.1% gel is better tolerated than tretinoin 0.025% gel in acne patients.

BACKGROUND: Adapalene is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. OBJECTIVE: We describe the results of a combined safety analysis of two multicenter trials conducted in the U.S. and Europe in which adapalene 0.1% gel was compared with tretinoin 0.025% gel in the treatment of mild to moderate acne vulgaris. METHODS: A total of 591 acne patients were enrolled in these investigator-masked, randomized, controlled, parallel group studies. In the two studies, each patient was randomly assigned to receive topical adapalene 0.1% gel or tretinoin 0.025% gel once daily at bedtime, for 12 weeks. In addition to assessments of efficacy and facial skin tolerance, data on adverse events were recorded at each visit or at any other time the patient reported problems. We extracted data concerning adverse reactions (i.e., adverse events judged to be related to the study treatment) from both studies and combined the results to obtain a global comparison of safety of the two products. RESULTS: A total of 15 of 296 patients (5.1%) reported 19 adverse reactions in the adapalene-treated groups, compared with 27 of 295 patients (9.1%) reporting 39 adverse reactions in the tretinoin-treated groups (p < 0.05). The number of patients discontinuing the study because of adverse events was approximately twice as low with adapalene (1.3% compared with 2.4%). Most adverse reactions for both products were related to skin irritation. No systemic adverse reactions were reported. CONCLUSION: The results of these two multicenter clinical studies indicate that adapalene gel is better tolerated than tretinoin gel.